CASE STUDY

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An approach to the patient with late-onset

cerebellar ataxia
Brent L Fogel and Susan Perlman*

S U M M A RY
Background An 83-year-old man presented with hypertension,

hyperlipidemia, and a previous basal cell carcinoma, having developed

progressive worsening of his balance and difficulty walking at the age
of 78 years. He was initially diagnosed with stroke, but MRI revealed
only isolated cerebellar atrophy. The patient then underwent multiple
evaluations for an underlying paraneoplastic process, all of which were
negative, but his symptoms progressed and he remained undiagnosed for
several years.
Investigations Neurological examination, laboratory blood tests, MRI,
and directed genetic testing.
Diagnosis Five years after becoming symptomatic, the patient was
re-evaluated for a possible genetic ataxia syndrome, which was
subsequently confirmed by gene testing as spinocerebellar ataxia type 6
(SCA6).
Management Symptomatic medical treatment and physical, occupational,
and speech therapy.
KEYWORDS ataxia, cerebellar, diagnosis, late onset, treatment

CME

BL Fogel is a resident physician in the Department of Neurology, and

S Perlman is a clinical professor of neurology and Director of the Ataxia
Center, University of California, Los Angeles, CA, USA.
Correspondence
*Department of Neurology, University of California, Los Angeles, 710 Westwood Plaza,
Los Angeles, CA 90095, USA
sperlman@mednet.ucla.edu
Received 19 June 2006 Accepted 15 August 2006
www.nature.com/clinicalpractice
doi:10.1038/ncpneuro0319

NOVEMBER 2006 VOL 2 NO 11

This article offers the opportunity to earn one

Category 1 credit toward the AMA Physicians
Recognition Award.
THE CASE

An 83-year-old man was referred to a tertiary

care ataxia center with a 5-year history of difficulty in walking and balance problems. He also
had a history of hypertension, hyperlipidemia,
and a basal cell carcinoma that had been treated
successfully with minor surgery 2 years previously. At the onset of his balance problems at
the age of 78 years, he had begun to stumble
and was unsteady on his feet. These symptoms
worsened progressively, and by a year later his
speech had also started to become dysarthric.
When the symptoms had first become noticeable,
the patient was evaluated in a local emergency
department and, on the basis of his clinical findings, was diagnosed with a mild stroke. An MRI
scan, however, showed no evidence of ischemia
but instead showed isolated cerebellar atrophy.
As the patients condition continued to worsen
he was referred to a neurologist, who initiated an evaluation for a paraneoplastic condition because of the patients previous history
of cancer. Investigations included CT scans of
the chest, abdomen, and pelvis; all results were
found to be unremarkable, and laboratory test
results for prostate-specific antigen, carcinoembryonic antigen, and the Hu, Ri, Ma, and
Ta serum neuronal antibodies were negative.
In addition, serum electrolytes, renal and liver
functions, and complete blood count were all
normal. Gliadin and glutamic acid decarboxylase 65 autoantibodies were negative, and rapid
plasma reagin was nonreactive. Serum protein
electrophoresis, alpha-fetoprotein, vitamin B12,
folate, parathyroid hormone, thyroid-stimulating
hormone, and vitamin E levels were all within
normal limits. MRI scans showed only cerebellar
degeneration. The patient was followed clinically, but over time he began to experience falls
and dysphagia, which eventually prompted his
referral to the ataxia center.

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On the basis of the patients clinical presentation and neurological examination findings as
well as his previous neuroimaging and diagnostic studies, a genetic ataxia syndrome was
considered. Given his lack of a family history of
ataxia, genetic evaluation was directed towards a
sporadic hereditary ataxic condition. This testing
was positive for a disease-associated CAG repeat
expansion in the gene for autosomal dominant
spinocerebellar ataxia (SCA) type 6, with 11
repeats on the normal allele and an abnormal
22 repeats on the affected allele.
The patient was treated empirically with
buspirone 5 mg twice daily, which was slowly
titrated to 15 mg twice daily over 4 weeks,
resulting in a mild subjective improvement in his
balance after 3 months. He was referred to physical, occupational, and speech therapy clinics for
gait retraining, assessment for an assistive device,
home safety, and management of his dysarthria
and dysphagia. Genetic counseling was also
offered to the patient and other family members
who were considered to be at risk.

DISCUSSION OF DIAGNOSIS

Figure 1 T1-weighted MRI brain scans of the

patient demonstrating diffuse atrophy isolated to
the cerebellum. (A) Coronal view. (B) Sagittal view.
The diffuse cerebellar atrophy is most severe in the
midline vermis (arrow).

The patient reported no family history of

ataxia or other neurological conditions, and
he had no history of excessive alcohol or drug
use, or exposure to toxic substances. On neurological examination, he demonstrated saccadic
smooth pursuit without nystagmus, mild ocular
dysmetria, scanning dysarthria, and moderate
appendicular and truncal ataxia. He also had
dysdiadochokinesia and a wide-based unstable
gait. Cognitive testing was normal and there
was no evidence of pyramidal or extrapyramidal signs, or any disturbances of sensation. An
MRI scan of the brain showed severe diffuse
cerebellar atrophy, which was most pronounced
in the midline vermis, without any involvement
of the brainstem or spinal cord (Figure 1).

630 NATURE CLINICAL PRACTICE NEUROLOGY

The patient in this case presented with what was

essentially a pure cerebellar phenotype without
additional associated features. His medical
and family histories were both unremarkable, and
although the presence of a history of cancer raised
the specter of a paraneoplastic syndrome, evaluation for this condition was also unilluminating.
Additional screening studies for acquired causes
were also unremarkable. As the patient had a negative family history for ataxic disorders, a sporadic
genetic mutation was considered; because of the
patients age and clinical examination, directed
genetic screening was initially confined to SCA6.
A previously published algorithm based on an
analysis of 127 patients with SCA18 suggests
a predictive value of 59% for SCA6 in similar
patients.1 It is important to note, however, that
in the general population of ataxic patients, additional, currently undescribed hereditary conditions are likely to exist; clinical studies examining
patients presenting with an idiopathic late-onset
pure cerebellar ataxia indicate that up to 70% may
have no currently identifiable genetic mutation.2
Fortunately, in this case, genetic testing yielded a
positive result and the diagnostic evaluation was
able to be successfully concluded.
SCA6 is a pure cerebellar ataxic syndrome
associated with a CAG repeat expansion within
the 1A subunit of the voltage-gated calcium
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channel encoded by the CACNA1A gene on

chromosome 19p13.35 Pathogenic alleles typically contain more than 21 CAG repeats.3,5,6 The
disease is characterized by a clinical phenotype
consisting primarily of cerebellar dysfunction
with gait and limb ataxia, dysarthria, and
nystagmus. Other findings such as neuropathy,
or pyramidal or extrapyramidal signs, are less
common but are occasionally seen.3,6 The age of
onset is approximately 50 years3,6 and the initial
cerebellar symptoms can be episodic. Evidence
suggests that affected patients have a normal
lifespan.3 A family history of ataxia is often not
reported in cases of SCA6, because the onset of
symptoms occurs later in life and symptoms are
often attributed to other medical conditions.3
Although not yet proven conclusively, there is
evidence that SCA6 might be a channelopathy.
As such, this disorder would be pathogenically
distinct from the majority of autosomal
dominant spinocerebellar ataxias, which
appear to be polyglutamate gain-of-function
diseases.3 Recently, SCA13 was identified as a
channelopathy arising from point mutations
in the gene encoding a cerebellar-enriched
voltage-gated potassium channel, KCNC3.7
SCA13 is an autosomal dominant syndrome
characterized by either adult-onset cerebellar
ataxia or early-onset ataxia and mental retardation.7 Once genetic testing is available, SCA13
will also be another important consideration in
the differential diagnosis of adult-onset ataxia.
The distinction between polyglutamate gain-offunction diseases and channelopathies could, in
addition, be important in the design of future
treatment strategies.7,8
DIFFERENTIAL DIAGNOSIS

The clinical finding of an insidious-onset

progressive cerebellar ataxia, as seen in the present
patient, can pose a significant diagnostic challenge. Ataxia as a general symptom can be seen in
a variety of diverse conditionsboth hereditary
and acquired. Obtaining a detailed description
of the onset and progression of symptoms is
an important initial step in differentiation. In an
adult, this process should include an in-depth
discussion of the patients previous activity levels
and coordination skills, because a slowly progressive ataxia can manifest itself subtly by way of a
reduction in a patients previous abilities, before
the onset of overt clinical symptoms. It is also
essential to obtain a detailed family history, and
it can often be useful to determine the patients

Table 1 Recommended primary clinical evaluation for acquired causes

of ataxia in an adult patient.
Differential diagnosisa

Investigation
Primary laboratory testing
Serum electrolytes

Metabolic abnormalities

Complete blood count

Lymphoproliferative disorders

Renal function

Renal disease

Liver function

Hepatic disease

Erythrocyte sedimentation rate (ESR)

Inflammation/vasculitis

Antinuclear antibody (ANA)

Systemic lupus erythematosus (SLE)/

rheumatologic disease

Rapid plasma reagin/fluorescein treponema

antibody (RPR/FTA)

Neurosyphilis

Thyroid-stimulating hormone

Hyperthyroidism/hypothyroidism

Glycated hemoglobin (HbA1c)

Glucose tolerance

Diabetes mellitus

Vitamin B12
Methylmalonic acid
Homocysteine

Subacute combined degeneration

Folate

Folate deficiency

Vitamin E

Vitamin E deficiency

Primary diagnostic studies

Brain MRI

Stroke
Subcortical vascular disease
Neoplasm
Structural anomaly
Multiple sclerosis (MS)
Normal pressure hydrocephalus
(NPH)
Leukodystrophy
CreutzfeldtJakob disease (CJD)
Neurodegeneration

Cervical, thoracic, and/or lumbar spine MRI

Multiple sclerosis (MS)

Structural anomaly
Myelopathy
Radiculopathy

Chest, abdomen, and/or pelvis CT

Malignancy

aSelected

differential diagnoses are shown in association with each test or study.

ethnic origin if possible, because some hereditary

ataxias have been found to show an increased
prevalence in certain geographic regions.3,9
The key features of cerebellar dysfunction
include dysmetric and saccadic eye movements
with nystagmus, dysarthria, a coarse kinetic
tremor, impaired coordination of targeted and
rapid-alternating movements (dysdiadochokinesia), and a wide-based unstable gait.9,10
The presence of additional features such as
dementia, behavioral changes, retinopathy, extrapyramidal features, upper motor neuron signs,
peripheral neuropathy, autonomic dysfunction,

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Table 2 Recommended secondary clinical evaluation for acquired causes of ataxia in an adult patient.
Tier denoting
frequency of use
in the evaluation

Secondary laboratory testinga

Differential diagnosisb

Secondary
diagnostic studiesa

Differential
diagnosisb

Ic

Angiotensin-converting enzyme (ACE)

Sarcoidosis

Ammonia

Liver failure/urea cycle defects

Electroencephalogram
(EEG)

Epilepsy/
CreutzfeldtJakob
disease (CJD)

Ceruloplasmin
Copper

Copper myelopathy,
Wilsons disease

Neuropathy

Creatine kinase (CK)

Myopathy

Fasting lipids

Cholesterol metabolic disorders

Electromyogram
(EMG)/nerve
conduction velocity
(NCV)

Lactate
Pyruvate

Mitochondrial disease

Serum/urine protein electrophoresis

(SPEP/UPEP)

Lymphoproliferative disorders

Somatosensory
evoked potential
(SSEP)/visual
evoked potential
(VEP)

Neurodegenerative/
demyelinating
disease

Serum ketones

Metabolic disorders

Urine heavy metals

Heavy metal toxicity

Antigliadin antibodies

Gluten-sensitive enteropathy

Anti-GAD65 antibodies

Stiff-person syndrome or variants

Autonomic testing/
orthostatics

Multiple system
atrophy

Anti-cerebellar antibodies
(Hu, Yo, Ri, Ma, Ta, CARP 8, CV2,
Tr, LEMS, mGluR1, CRMP5, GQ1b,
amphiphysin, PCA-2, and others)

Paraneoplastic cerebellar ataxia

FDG-PET scan

Metabolic disorders

Muscle biopsy

Mitochondrial
disease

Human T-cell lymphotropic virus

type I/II (HTLV I/II)

Human T-cell lymphotropic virus

(HTLV)-associated myelopathy

HIV

HIV-associated neurological disease

Lyme titers

Lyme-associated neurological disease

SSA/SSB antibodies

Sjgrens syndrome

Cerebrospinal fluid (CSF) analysis

(protein, cell count, glucose, cultures,
venereal disease research laboratory
[VDRL], IgG synthesis, oligoclonal
bands, cytology, lactate, 14-3-3
protein, paraneoplastic antibodies,
and other selected tests)

CreutzfeldtJakob disease (CJD),

encephalitis, immune-mediated
polyneuropathy, inborn errors of
metabolism, mitochondrial disease,
multiple sclerosis (MS), neoplasm,
neurosyphilis, paraneoplastic
cerebellar ataxia, Whipples disease

[18F]fluoro-L-DOPA
(FDOPA)-PET scan

Parkinsons disease

Magnetic resonance
spectroscopy

Metabolic disorders

Nerve biopsy

Neuropathy

Lysosomal screen

Lysosomal storage disease

Bone marrow biopsy

Plasma amino acids

Urine organic acids

Inborn errors of metabolism

Lymphoproliferative
disorders

Brain biopsy

Prion disease

Very long chain fatty acids

Peroxisomal disorders

Conjunctival or skin
biopsy

Storage disorders

IId

IIId

IVe

aNote that not all patients will require all tests or studies listed, and the evaluation should be guided by clinical phenotype and neurological examination.
bSelected differential diagnoses are shown in association with each test or study. cIncludes general tests and common studies that will be required by most
patients with a normal initial screen. dIncludes autoimmune/infectious and cerebrospinal fluid tests, as well as more-specific diagnostic tests that may be
required in certain patients. eIncludes tests and studies that are only useful in specific subsets of ataxia patients. Abbreviations: anti-GAD65; anti-glutamic acid

decarboxylase 65; FDG, fluorodeoxyglucose; SSA/SSB, Sjgrens syndrome antigen.

and seizures, can be useful for differentiating

ataxic etiologies.9,10
The initial diagnostic evaluation of an ataxic
patient should include an in-depth assessment
for potential acquired causes.8 This screening

632 NATURE CLINICAL PRACTICE NEUROLOGY

should always be performedeven in the setting

of a suspected hereditary ataxiabecause
acquired and hereditary causes can coexist. In
the older ataxic patient, multifactorial disease
is relatively common and is often the rule.

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Table 3 Recommended genetic considerations for ataxia in an adult patient.a

Phenotype

Genetic considerations

Patient over age 40 years at onset of symptoms

Spinocerebellar ataxia type 6 (SCA6)b

Fragile X-associated tremorataxia syndrome

Autosomal dominant inheritance or sporadic onset

Spinocerebellar ataxia type 1 (SCA1)b

Spinocerebellar ataxia type 2 (SCA2)b
Spinocerebellar ataxia type 3 (SCA3)b
Spinocerebellar ataxia type 5 (SCA5)b
Spinocerebellar ataxia type 7 (SCA7)b
Spinocerebellar ataxia type 8 (SCA8)b
Spinocerebellar ataxia type 10 (SCA10)b
Spinocerebellar ataxia type 12 (SCA12)b
Spinocerebellar ataxia type 14 (SCA14)b
Spinocerebellar ataxia type 17 (SCA17)b
Dentatorubral-pallidoluysian atrophy (DRPLA)

Autosomal recessive inheritance or sporadic onset

Friedreichs ataxia
Ataxia with oculomotor apraxia type 1 (AOA1)
Ataxia with oculomotor apraxia type 2 (AOA2)
TaySachs disease

Others, including maternal or X-linked inheritance patterns

Metabolic disordersc
Mitochondrial disordersc
Leukodystrophiesc

aSelected

hereditary syndromes to consider in an adult patient with progressive ataxia are shown. The selection of tests
to perform should be directed towards the patients phenotype, neurological features, and previous diagnostic evaluation.
Not all available genetic tests for hereditary ataxias are listed. See also Supplementary Table 1 online for a list of internet
sites that might be useful in the selection of genetic tests for individual patients. bNote that spinocerebellar ataxias can be
phenotypically heterogeneous, thus the subtypes listed are those with genetic testing available. cSpecific tests vary and are
dependant on clinical phenotype.

In rare instances multiple genetic mutations can

even coexist, and, if suspected, these should be
given consideration. An algorithm for a focused
screening evaluation is proposed in Tables 13.
Such screening should always include neuroimaging of the brainideally with MRIas this
can rapidly identify confounding entities such as
stroke, neoplasm, demyelinating disease, trauma,
or cerebellar anomalies. Some hereditary or
acquired ataxic conditions such as Wilsons
disease, leukodystrophies, or prion disease
can also demonstrate characteristic degenerative features on MRI scans. The predominant
MRI finding in patients with spinocerebellar
ataxia is atrophy of the cerebellum or olivopontocerebellar structures.3 After the initial
screening evaluation (Table 1), the need for
additional studies (Table 2) can be determined
on the basis of the patients clinical history and
neurological examination findings.
If a detailed screening for acquired causes
is found to be negative, the diagnostic evaluation can then be directed towards hereditary
or sporadic genetic etiologies (Table 3, and
Supplementary Table 1 online). Various flowcharts have been developed to guide directed

gene testing, particularly for the autosomal

dominant spinocerebellar ataxias, which allow
differentiation on the basis of predominant
clinical features.3 For the most common autosomal dominant SCAstypes 18a clinically
based mathematical algorithm has recently been
developed to direct gene testing,1 which can be
useful in initial screening for a hereditary condition. Because of the rapid pace of molecular
genetic research, new genetic tests frequently
become available, so patients with unidentified but suspected hereditary ataxia should be
periodically re-evaluated with updated genetic
screening. At least 24 autosomal dominant
hereditary ataxias have been described,3,4 in
addition to at least half as many autosomal recessive disorders.4,11 Age of symptom onset can be
a key distinguishing feature of the two types, as
most recessive ataxic syndromes are early-onset
and tend to present before the age of 20 years,11
and most dominant ataxias typically present
later in life.3 This distinction is not absolute,
however, and some patients with Friedreichs
ataxia or TaySachs disease, for example, can
present clinically much later then expected.12,13
It has been suggested that late-onset ataxia

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Table 4 Potential therapeutic treatments for various symptoms of cerebellar dysfunction.

Symptom

Medicationa

Suggested dosageb

Selected referencec

Cerebellar ataxia

Amantadine
Buspirone
L-Tryptophan
Acetazolamide
Branched-chain amino acids
D-Cycloserine

25150 mg b.i.d.
530 mg b.i.d.
6001,000 mg q.d.
4 g/day b.i.d.q.i.d.
1.53.0 g q.d.
25 mg b.i.d.

Botez et al. (1996)

Trouillas et al. (1997)
Trouillas et al. (1995)
Yabe et al. (2001)
Mori et al. (2002)
Ogawa et al. (2003)

Cerebellar tremor

Primidone
Propranolol
Clonazepam
Carbamazepine
Ondansetron
Valproate
Zonisamide
Topiramate
Levetiracetam

Up to 500 mg t.i.d.
Up to 240 mg/day
0.52.0 mg q.d.
100400 mg t.i.d.
Up to 48 mg t.i.d.
250 mg q.d.1,000 mg b.i.d.
100 mg q.d.300 mg b.i.d.
25100 mg b.i.d.
Up to 50 mg/kg/day

Koller et al. (1989)

Koller et al. (1989)
Sandyk (1985)
Sechi et al. (1989)
Rice et al. (1997)
Ikeda et al. (1990)
Morita et al. (2005)
Sechi et al. (2003)
Striano et al. (2006)

Central nystagmus

Clonazepam
Baclofen
Gabapentin
Aminopyridines

0.52.0 mg q.d.
Up to 40 mg t.i.d.
3001,600 mg t.i.d.
Varies by compound; up to 80 mg/day for
3,4 diaminopyridine (3,4-DAP)
520 mg/day

Currie and Matsuo (1986)

Dieterich et al. (1991)
Averbuch-Heller et al. (1997)
Strupp et al. (2003)

Memantine

Shery et al. (2006)

aPlease note that none of these medications has FDA approval in the US for use in this capacity. bDosages are suggestions compiled from review of multiple
studies8 in addition to personal experience, and may not reflect the dosages used in the selected reference. cReferences indicate selected publications

describing or supporting the use of the medication for the associated condition. Complete reference listings are provided in Supplementary Reference List 1
online. Abbreviations: b.i.d., twice daily; q.d., once daily; q.i.d., four times daily; t.i.d., three times daily.

should be defined as that occurring after the age

of 40 years.2 Although there is much overlap, this
distinction can be useful diagnostically, since of
all the known hereditary ataxias only SCA6, a
predominantly cerebellar syndrome, and fragile
X-associated tremorataxia syndrome, have a
clear mean age of onset well beyond 40 years of
age.3,4,11,14 In the older male (and occasional
female) without an obvious family history, the
late-onset phenotype of fragile X-associated
tremorataxia syndrome consisting of gait ataxia,
tremor, parkinsonism, and cognitive dysfunction,
could be misdiagnosed as another more common
neurological illness, such as dementia, essential
tremor, Parkinsons disease, or stroke.14
Multiple system atrophy (MSA) is an important consideration in a patient presenting
with a late-onset ataxic phenotype. MSA is
a sporadic progressive neurodegenerative
condition characterized primarily by cerebellar dysfunction, parkinsonism, autonomic
dysfunction, and pyramidal signs.15 Diagnostic
guidelines are currently based on clinical evaluation, because other investigative studies can be
equivocal early in the disease course.15 Studies
such as MRI, functional imaging, anal sphincter
electromyogram, or autonomic studies can be

634 NATURE CLINICAL PRACTICE NEUROLOGY

useful in specific cases to differentiate MSA

from other neurodegenerative diseases.15 Prion
diseases are another important consideration
in patients with a late-onset ataxic phenotype. These neurodegenerative spongiform
encephalopathies can be sporadic, acquired,
or familial.16 Clinically, most patients exhibit
a rapidly progressive dementia with additional
neurological signs, but some casesparticularly
those with sporadic CreutzfeldtJakob disease
or familial GerstmannStrusslerScheinker
diseasecan present with a late-onset ataxic
phenotype.16 A definitive diagnosis is achieved
only by laboratory pathology investigations,
although electroencephalogram and cerebrospinal fluid studies can support a diagnosis,16
and MRIin particular diffusion-weighted and
fluid-attenuated inversion recovery images
can also be helpful.
In sporadic cases of late-onset cerebellar
ataxia that are found to lack a specific acquired
or genetic etiology after detailed evaluation,
a diagnosis of idiopathic late-onset cerebellar
ataxia can also be considered.17 In one large
study that assessed over 100 such patients for
likely alternative etiologies, fewer than 30%
met the criteria for MSAeven after 4 years

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of disease symptomsand fewer than 15%

were ultimately found to have an identifiable
genetic cause, leaving nearly 60% diagnosed
as idiopathic.17 Continued surveillance and
periodic re-evaluation of these patients could
be warranted, however, as it remains possible
that at least some patients might have an
as-yet-undetermined genetic cause.2,17

physical examination, as well as a focused and

directed diagnostic evaluation for acquired
and hereditary etiologies. In a patient over the
age of 40 years with sporadic progressive ataxia,
SCA6 is an important consideration. Treatment
of hereditary ataxia is generally symptomatic and
should be focused on maximizing the patients
functionality while preventing physical, social,
and psychological complications.

Competing interests
The authors declared that
they have no competing
interests.

THERAPEUTIC MANAGEMENT

Much of the treatment currently available for

late-onset hereditary ataxia is unfortunately
only symptomatic. The most prominent feature,
ataxia, is notoriously difficult to manage, and
to date there are no clearly effective treatments
available,3 and no medications have received
FDA approval for use in the US in this capacity.8
A number of small clinical trials have studied
various medications for the symptomatic treatment of ataxia and the associated features seen
in hereditary ataxic conditions,8 in addition
to antioxidants for their potential as neuroprotectants.8 Medications that have previously been reported to be of benefit for the
therapeutic management of the most common
cerebellar symptoms are indicated in Table 4,
along with suggestions for their use (see also
Supplementary Reference List 1 online). It is
hoped that future studies will uncover more
effective medical therapies, and more novel
therapeutic strategies such as RNA interference
could soon become feasible.18 For now, patients
will benefit most from a comprehensive plan
that addresses both the neurological and practical symptoms of their disease.8 For falls and
ambulation difficulties, physical and occupational therapies can provide assistance in
strengthening muscles that support the trunk,
and also provide gait and balance retraining.
Assistive devices that maximize functional independence and home safety are other important
considerations. Speech therapy can be used to
improve dysarthria and dysphagia if present.
Social workers, genetic counselors, psychologists, and psychiatrists can also be instrumental
in helping patients and their families to cope
with issues surrounding their progressively
worsening condition.
CONCLUSION

The patient presenting with a late-onset progressive ataxic phenotype poses a diagnostic challenge to the clinician, which can be addressed
by means of a thorough medical history and

Supplementary information in the form of a

table and a reference list is available on the Nature
Clinical Practice Neurology website.
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6 Takahashi H et al. (2004) A clinical and genetic study in
a large cohort with spinocerebellar ataxia type 6.
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7 Waters MF et al. (2006) Mutations in voltage-gated
potassium channel KCNC3 cause degenerative and
developmental central nervous system phenotypes.
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genetic classification of inherited ataxias. II: autosomal
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phenotypic analysis, magnetic resonance imaging
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13 Neudorfer O et al. (2005) Late-onset Tay-Sachs disease:
phenotypic characterization and genotypic correlations
in 21 affected patients. Genet Med 7: 119123
14 Hall DA et al. (2005) Initial diagnoses given to persons
with the fragile X associated tremor/ataxia syndrome
(FXTAS). Neurology 65: 299301
15 Wenning GK et al. (2004) Multiple system atrophy.
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16 Ironside JW et al. (2005) Phenotypic variability in
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2006 Nature Publishing Group